An effective vaccine against human immunodeficiency virus type 1 (HIV-1) infection must incorporate features necessary to neutralize variant viral subtypes present in different parts of the world. South Asia, particularly India, is currently recording the steepest increases in new HIV-1 infections. The predominant strains infecting patients in India, as also parts of Africa, is subtype C. It has been estimated that subtype C infections account for about 50 percent of global HIV-1 infections. Yet, little is known about the biological properties of these viruses. Better characterization of HIV-1 has important implications for the development of prevention strategies because it should be targeted at the properties of viruses involved in transmission, pathogenicity and disease progression. We hypothesize that there are specific properties of HIV-1, including the functional domains in the env gp120 that are critical determinants of transmission and pathogenesis of infection. In this AIDS-FIRCA grant, it is proposed to study the biological properties of HIV-1, including replication efficiency cellular tropism, co-receptor usage, cytopathic effects, and genotypic and phenotypic properties involved in mother-to-child transmission of subtype HIV-1 C isolates obtained from patients in India. This will be accomplished by: (1) constructing proviral chimeras and recombinant viruses containing eng gp120 from HIV-1 subtype C in the background of an HIV-1 subtype B infectious molecular clone, pNL4-3, and (2) using the recombinant viruses so generated to infect T-lymphocyte lines and primary cells (primary blood lymphocytes and monocytes/macrophages), and reporter cell lines containing CD4 and various co-receptors. The ability of recombinant viruses to infect cell lines and primary cells of different lineages, their ability to induce syncytia, and a comparison to well characterized HIV-1 isolates will help understand the biological properties of HIV-1 subtype C viruses mediated by env gp120. An analysis of mother-infant pairs will provide information on properties conducive to perinatal transmission and test the hypothesis proposed by the P.I. about transmission of minor variants in a non-B subtype background. The information obtained may be useful in designing vaccination strategies againts HIV-1 subtype C and in developing intervention strategies to limit its perinatal transmission.